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β-Arrestin 2 knocko...
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Björk, KarlKarolinska Institutet
(author)
β-Arrestin 2 knockout mice exhibit sensitized dopamine release and increased reward in response to a low dose of alcohol
- Article/chapterEnglish2013
Publisher, publication year, extent ...
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2013-06-19
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Springer,2013
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Numbers
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LIBRIS-ID:oai:DiVA.org:liu-94653
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-94653URI
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https://doi.org/10.1007/s00213-013-3166-xDOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:127776655URI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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RationaleThe rewarding effects of alcohol have been attributed to interactions between opioid and dopaminergic system within the mesolimbic reward pathway. We have previously shown that ablation of β-arrestin 2 (Arrb2), a crucial regulator of μ-opioid receptor function, attenuates alcohol-induced hyperlocomotion and c-fos activation in the nucleus accumbens.ObjectivesHere, we further investigated the role of Arrb2 in modulating alcohol-induced dopamine (DA) release and conditioned place preference (CPP). We also assessed the functional importance of Arrb2 for μ-opioid receptor surface expression and signaling following an acute alcohol challenge.MethodsAlcohol-evoked (0.375, 0.75, and 1.5 g/kg intraperitoneally) DA release was measured by in vivo microdialysis in the shell of nucleus accumbens. Reward was assessed by the CPP paradigm. Receptor function was assessed by μ-receptor binding and [35S]GTP-γ-S autoradiography.ResultsIn Arrb2 knockout mice accumbal DA levels reach maximum response at a lower dose compared to wild-type (wt) animals. In line with these results, Arrb2 knockout mice display increased CPP for alcohol as compared to wt mice. Finally, Arrb2 mutant mice display increased μ-opioid receptor signaling in the ventral and dorsal striatum and amygdala in response to a low dose of alcohol, indicating impaired desensitization mechanisms in these mice.ConclusionsOur results show that Arrb2 modulates the response to low doses of alcohol on various levels including μ-opioid receptor signaling, DA release, and reward. They also reveal a clear dissociation between the effects of Arrb2 on psychomotor and reward behaviors.
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Tronci, ValeriaPsychobiology Section, NIDA, National Institutes of Health, Baltimore, MD, USA
(author)
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Thorsell, AnnikaLinköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Centrum för social och affektiv neurovetenskap (CSAN)(Swepub:liu)annth96
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Tanda, GianluigiPsychobiology Section, NIDA, National Institutes of Health, Baltimore, MD, USA
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Hirth, NatalieUniversity of Heidelberg, Mannheim, Germany
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Heilig, MarkusLaboratory of Clinical and Translational Studies, NIAAA, National Institutes of Health, Bethesda, MD, USA(Swepub:liu)marhe41
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Hansson, Anita C.Laboratory of Clinical and Translational Studies, NIAAA, National Institutes of Health, Bethesda, MD, USA
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Sommer, Wolfgang HLaboratory of Clinical and Translational Studies, NIAAA, National Institutes of Health, Bethesda, MD, USA
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Karolinska InstitutetPsychobiology Section, NIDA, National Institutes of Health, Baltimore, MD, USA
(creator_code:org_t)
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In:Psychopharmacology: Springer230:3, s. 439-4490033-31581432-2072
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